'Clinical Trial' is a research study in which a new drug is tested on humans for its safety and efficacy regarding a particular disease. In March 2006, such a trial was conducted in London where the test drug named TGN1412 left 6 healthy participants with life-threatening illnesses. This infamous clinical trial was named 'The Elephant Drug Trial'. The incident caused shockwaves amongst the medical and pharmaceutical communities.
What was TGN1412?
TGN1412 was a novel monoclonal antibody developed by a German biotech firm named TeGenero. It was intended to be used for the treatment of leukemia and auto-immune diseases.
Scientists had high hopes for this drug as it showed no side effects in monkeys when the drug was injected. Hence, the next step of this trial was to conduct Phase-1 in which a test drug was to be tested on human beings.
What was 'The Elephant Man' drug trial?
On 13th March 2006, 8 healthy men took part in the Phase-1 trial of TGN1412, organized by US company Parexel at an independent unit at Northwick Park Hospital in North-West London.
Out of 8 volunteers, 6 were injected with a test drug and the remaining 2 were injected with a harmless placebo. Neither participants nor the medical staff knew who got what as it was a blinded trial.
The test drug was administered to 6 men by intravenous infusion over the course of 3 to 6 minutes. The drug given to the participants was 10 times faster than it had been in animals.
Within one hour of drug administration, the horror of the trial started. 2 lucky participants who received the placebo instead of TGN1412 witnessed the terrible incident as 6 of their fellow participants suddenly became very ill. This event was infamously known as 'The Elephant Man Trial' due to comments made by one of the participants that got published in media reports.
What exactly happened to the volunteers of this trial?
Within a few minutes, the first participant experienced severe headache, muscle pain, nausea, vomiting, diarrhea, high fever, restlessness, swollen head, rash, etc. After a few hours, all 6 participants who got the test drug experienced hypotension, tachycardia, and the onset of respiratory failure. Medical staff panicked as one by one, all the patients collapsed.
The next day, all 6 people were transferred to the ICU. Then their symptoms progressed to organ failure. Later, it was found that the test drug, TGN1412, caused a 'cytokine storm' in the volunteers. It was an extreme and near-fatal immune response.
These participants were given high doses of steroids and kept alive by life support machines. They were all hospitalized for about 3-6 weeks and later discharged with a warning that they may suffer an increased risk of cancer and other auto-immune diseases.
Nav Modi of East London, who was 24 years old at the time of the trial said that he felt like somebody had put his brain on fire. He also shared that his head had swollen-up like that of an elephant's. Hence, the media named this whole incident as, ‘The Elephant Man Drug Trial.’ David Okaley, the very first person to receive the test drug, recalled the whole incident and said that he was left feeling like an '80-years old man'. His muscles were completely damaged. "It was pretty scary to see somebody you love so disfigured," said Katrina, fiancée of David.
What were the long-term side effects of the test drug on participants?
Ryan Wilson, one of the participants, almost died due to multi-organ failure. Initially, the doctors thought that there was no hope for his survival. He fell into a coma. But miraculously, he did survive. Though later, he still had to go through many surgeries to repair the damage done to his body by the test drug. His body failed to recover completely.
Other participants experienced prolonged weakness and vulnerability to various infections. They were totally unaware of future complications that might happen to their body over a course of time.
Did anything change after this incident?
This incident shook the whole of Europe. The Medicine and Healthcare Products Regulatory Authority (MHRA) started an investigation. In its report, it was found that the German Biotech firm, TeGenero, had inadequate insurance and was shut down after this disastrous incident. The other company that conducted the trial, Parexel, refused to accept joint liability at first. Later, Parexel agreed to a settlement and paid undisclosed compensation to the volunteers. Even clinicians had not considered the safe dosage of the drug for humans.
This report of MHRA led to a further deep investigation and another report with 22 new recommendations about Phase-1 trial (in humans) was published. One of those recommendations is that drug trials should not give a new drug to many participants on the same day and a safe dose of new medicine needs to be considered in Phase-1. All these recommendations now apply throughout Europe and even the world.
What lesson did we get from this horrific trial?
We can not rule out the use of humans in drug trials. At some stage, during a trial, a human will always have to be the first to receive a test drug. We can not avoid the risks associated with it. The report released by MHRA in 2015 says that 7,187 participants in clinical trials had suffered serious and unexpected adverse drug reactions. 493 of those adverse reactions were immediately life-threatening and 197 caused significant disability. Hence, appropriate insurance and compensation to the participants play a very important role in conducting clinical trials.
Clinical trials benefit us. Without them, various new life-saving drugs would not exist. Yet when something goes wrong, we have to pay for the human cost, which can be very high. This individual may suffer throughout his life due to side effects of the new drug. Hence, we need to insist and advocate for safe clinical trials and adequate atonement.
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